S0148 |
HAMNO
|
HAMNO (NSC-111847) is a potent and selective replication protein A (RPA) inhibitor with anti-tumor activity. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. |
|
|
S1009 |
Dactolisib (BEZ235)
|
Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2. |
-
Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
-
Cancer Res, 2022, canres.2609.2021
-
Cell Death Dis, 2022, 13(2):146
|
|
S1092 |
KU-55933 (ATM Kinase Inhibitor)
|
KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/Ki of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR. KU‑55933 (ATM Kinase Inhibitor) inhibits the activation of autophagy‑initiating kinase ULK1 and results in a significant decrease of autophagy. |
-
Nat Commun, 2022, 13(1):360
-
Cancer Res, 2022, canres.2229.2021
-
Elife, 2022, 11e70518
|
|
S1570 |
KU-60019
|
KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer. |
-
EMBO Rep, 2022, 23(2):e53658
-
Cell Rep, 2022, 38(2):110216
-
Cell Biosci, 2022, 12(1):43
|
|
S2245 |
CP-466722
|
CP-466722 is a potent and reversible ATM inhibitor, does not affect ATR and inhibits PI3K or PIKK family members in cells. |
-
G3 (Bethesda), 2020, 4;10(5):1585-1597
-
Cell, 2019, 36(2):179-193
-
Cancer Cell, 2019, 36(2):179-193
|
|
S2758 |
Wortmannin (KY 12420)
|
Wortmannin (KY 12420, SL-2052, BRN 0067676, NSC 627609) is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity. |
-
Cancer Res, 2022, canres.2292.2021
-
Cell Rep, 2022, 38(11):110522
-
Proc Natl Acad Sci U S A, 2022, 119(3)e2114134119
|
|
S2817 |
Torin 2
|
Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM,in PC3 cell lines respectively. Torin 2 decreases cell viability and induces autophagy and apoptosis. |
-
Adv Sci (Weinh), 2022, 10.1002/advs.202104055
-
Cancer Res, 2022, canres.1397.2021
-
Mol Cancer Ther, 2022, molcanther.MCT-21-0947-A.2021
|
|
S3600 |
Schisandrin B (Sch B)
|
Schisandrin B is the most abundant dibenzocyclooctadiene lignan present in the traditional Chinese medicinal herb Schisandra chinensis (Turcz.) Baill. It is a kind of ATR and P-gp inhibitor with high safety. |
-
Ann Transl Med, 2021, 9(19):1500
-
Drug Dev Res, 2021, 10.1002/ddr.21905
-
Pharmacol Res, 2021, 166:105459
|
|
S7050 |
AZ20
|
AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR. |
-
J Med Chem, 2022, 65(5):4182-4200
-
Sci Rep, 2022, 12(1):5827
-
Nat Commun, 2021, 12(1):4856
|
|
S7136 |
CGK 733
|
CGK 733 is a potent and selective inhibitor of ATM/ATR with IC50 of ~200 nM. |
-
Aging (Albany NY), 2021, 13(8):11705-11726
-
mBio, 2020, 11(1)
-
Mol Cells, 2016, 39(12):869-876
|
|
S7693 |
Ceralasertib (AZD6738)
|
Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.
|
-
Cancer Cell, 2022, S1535-6108(21)00662-0
-
Dev Cell, 2022, 57(5):638-653.e5
-
Cancer Res, 2022, canres.1707.2021
|
|
S8007 |
VE-821
|
VE-821 is a potent and selective ATP competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ. |
-
EMBO J, 2022, 10.15252/embj.2021108599
-
FASEB J, 2022, 36(3):e22221
-
Sci Signal, 2022, 15(715):eabh2290
|
|
S8050 |
ETP-46464
|
ETP-46464 is a potent and selective inhibitor of ATR with IC50 of 25 nM. |
-
Nat Commun, 2019, 10(1):5718
-
Nat Commun, 2019, 10(1):3585
-
Oncogenesis, 2019, 8(7):38
|
|
S8096 |
Mirin
|
Mirin is a potent Mre11–Rad50–Nbs1 (MRN) complex inhibitor, and inhibits Mre11-associated exonuclease activity. Mirin inhibits MRN-dependent activation of ATM. |
-
NAR Cancer, 2022, 4(2):zcac012
-
Mol Cell, 2021, S1097-2765(21)00390-7
-
Mol Cancer Ther, 2021, 20(9):1561-1571
|
|
S8375 |
AZD0156
|
AZD0156 is a potent and selective inhibitors of ATM kinase, with potential chemo-/radio-sensitizing and antineoplastic activities. AZD0156 prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells. |
-
Sci Transl Med, 2022, 14(638):eabc7480
-
Cell Rep, 2022, 38(2):110216
-
Int J Mol Sci, 2022, 23(7)3834
|
|
S8556 |
AZ31
|
AZ31 is a selective and novel ATM inhibitor with an IC50 of <0.0012 μM. It shows excellent selectivity over closely related enzymes (>500 fold selective over DNA-PK and PI3Kα and >1000 fold selective over mTOR, PI3Kβ and PI3Kγ). |
-
Proc Natl Acad Sci U S A, 2020, 117(50):31891-31901
|
|
S8666 |
Elimusertib (BAY-1895344) hydrochloride
|
Elimusertib (BAY-1895344) hydrochloride is a potent, highly selective and orally available ATR inhibitor with an IC50 of 7 nM. |
-
Clin Cancer Res, 2021, clincanres.1010.2021
-
Cancer Res, 2021, 81(18):4676-4684
-
Cancer Discov, 2021, 11(2):362-383
|
|
S8680 |
AZD1390
|
AZD1390 is a first-in-class orally available and CNS penetrant ATM inhibitor with an IC50 of 0.78 nM in cells and >10,000-fold selectivity over closely related members of the PIKK family of enzymes and excellent selectivity across a broad panel of kinases. |
-
Cancer Cell, 2022, S1535-6108(21)00662-0
-
Sci Transl Med, 2022, 14(638):eabc7480
-
Nucleic Acids Res, 2022, 50(5):2700-2718
|
|
S8729 |
AZ32
|
AZ32 is a specific inhibitor of the ATM kinase that possesses good BBB penetration in mouse with an IC50 value of <0.0062 μM for ATM enzyme. It shows adequate selectivity over ATR and also has high cell permeability. |
|
|
S9639 |
VX-803 (M4344)
|
VX-803 (M4344, ATR inhibitor 2) is an ATP-competitive, orally active, and selective inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase with Ki of < 150 pM. VX-803 (M4344) potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. VX-803 (M4344) exhibits potential antineoplastic activity. |
|
|
S9864 |
Elimusertib (BAY-1895344)
|
Elimusertib (BAY-1895344) is a very potent and highly selective ATR (ataxia telangiectasia and Rad3-related) inhibitor with IC50 of 7 nM. Elimusertib potently inhibits proliferation of a broad spectrum of human tumor cell lines with median IC50 of 78 nM. |
-
J Med Chem, 2022, 65(5):4182-4200
-
Sci Rep, 2022, 12(1):5827
-
Nat Commun, 2021, 12(1):6813
|
|
S3224 |
Cinobufagin
|
Cinobufagin (Cinobufagine), an active ingredient of Venenum Bufonis, inhibits tumor development. Cinobufagin increases ATM and Chk2 and decreases CDC25C, CDK1, and cyclin B. Cinobufagin inhibits PI3K, AKT and Bcl-2 while increases levels of cleaved caspase-9 and caspase-3. Thus, Cinobufagin induces cell cycle arrest at the G2/M phase and apoptosis. |
|
|
S4157 |
Chloroquine diphosphate
|
Chloroquine diphosphate is a 4-aminoquinoline anti-malarial and anti-rheumatoid agent, also acting as an ATM activator. Chloroquine is also an inhibitor of toll-like receptors (TLRs). |
-
Bioact Mater, 2022, 18:459-470
-
Phytomedicine, 2022, 98:153958
-
Bone, 2022, 154:116262
|
|
S6885 |
Ailanthone
|
Ailanthone (AIL, Δ13-Dehydrochaparrinone), a natural anti-hepatocellular carcinoma (HCC) component in Ailanthus altissima, induces G0/G1-phase cell cycle arrest by decreasing expression of cyclins and CDKs and increases expression of p21 and p27. Ailanthone triggers DNA damage characterized by activation of the ATM/ATR pathway. Ailanthone induces apoptosis which is mitochondrion-mediated and involves the PI3K/AKT signaling pathway in Huh7 cells. Ailanthone is also a potent inhibitor of both full-length Androgen Receptor (AR-FL) and constitutively active truncated AR splice variants (AR-Vs, AR1-651) with IC50 of 69 nM and 309 nM, respectively. |
|
|
S0148 |
HAMNO
|
HAMNO (NSC-111847) is a potent and selective replication protein A (RPA) inhibitor with anti-tumor activity. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. |
|
|
S1009 |
Dactolisib (BEZ235)
|
Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2. |
- Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7
- Cancer Res, 2022, canres.2609.2021
- Cell Death Dis, 2022, 13(2):146
|
|
S1092 |
KU-55933 (ATM Kinase Inhibitor)
|
KU-55933 (ATM Kinase Inhibitor) is a potent and specific ATM inhibitor with IC50/Ki of 12.9 nM/2.2 nM in cell-free assays, and is highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR. KU‑55933 (ATM Kinase Inhibitor) inhibits the activation of autophagy‑initiating kinase ULK1 and results in a significant decrease of autophagy. |
- Nat Commun, 2022, 13(1):360
- Cancer Res, 2022, canres.2229.2021
- Elife, 2022, 11e70518
|
|
S1570 |
KU-60019
|
KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer. |
- EMBO Rep, 2022, 23(2):e53658
- Cell Rep, 2022, 38(2):110216
- Cell Biosci, 2022, 12(1):43
|
|
S2245 |
CP-466722
|
CP-466722 is a potent and reversible ATM inhibitor, does not affect ATR and inhibits PI3K or PIKK family members in cells. |
- G3 (Bethesda), 2020, 4;10(5):1585-1597
- Cell, 2019, 36(2):179-193
- Cancer Cell, 2019, 36(2):179-193
|
|
S2758 |
Wortmannin (KY 12420)
|
Wortmannin (KY 12420, SL-2052, BRN 0067676, NSC 627609) is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity. |
- Cancer Res, 2022, canres.2292.2021
- Cell Rep, 2022, 38(11):110522
- Proc Natl Acad Sci U S A, 2022, 119(3)e2114134119
|
|
S2817 |
Torin 2
|
Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM,in PC3 cell lines respectively. Torin 2 decreases cell viability and induces autophagy and apoptosis. |
- Adv Sci (Weinh), 2022, 10.1002/advs.202104055
- Cancer Res, 2022, canres.1397.2021
- Mol Cancer Ther, 2022, molcanther.MCT-21-0947-A.2021
|
|
S3600 |
Schisandrin B (Sch B)
|
Schisandrin B is the most abundant dibenzocyclooctadiene lignan present in the traditional Chinese medicinal herb Schisandra chinensis (Turcz.) Baill. It is a kind of ATR and P-gp inhibitor with high safety. |
- Ann Transl Med, 2021, 9(19):1500
- Drug Dev Res, 2021, 10.1002/ddr.21905
- Pharmacol Res, 2021, 166:105459
|
|
S7050 |
AZ20
|
AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR. |
- J Med Chem, 2022, 65(5):4182-4200
- Sci Rep, 2022, 12(1):5827
- Nat Commun, 2021, 12(1):4856
|
|
S7136 |
CGK 733
|
CGK 733 is a potent and selective inhibitor of ATM/ATR with IC50 of ~200 nM. |
- Aging (Albany NY), 2021, 13(8):11705-11726
- mBio, 2020, 11(1)
- Mol Cells, 2016, 39(12):869-876
|
|
S7693 |
Ceralasertib (AZD6738)
|
Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.
|
- Cancer Cell, 2022, S1535-6108(21)00662-0
- Dev Cell, 2022, 57(5):638-653.e5
- Cancer Res, 2022, canres.1707.2021
|
|
S8007 |
VE-821
|
VE-821 is a potent and selective ATP competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM in cell-free assays, shows inhibition of H2AX phosphorylation, minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ. |
- EMBO J, 2022, 10.15252/embj.2021108599
- FASEB J, 2022, 36(3):e22221
- Sci Signal, 2022, 15(715):eabh2290
|
|
S8050 |
ETP-46464
|
ETP-46464 is a potent and selective inhibitor of ATR with IC50 of 25 nM. |
- Nat Commun, 2019, 10(1):5718
- Nat Commun, 2019, 10(1):3585
- Oncogenesis, 2019, 8(7):38
|
|
S8096 |
Mirin
|
Mirin is a potent Mre11–Rad50–Nbs1 (MRN) complex inhibitor, and inhibits Mre11-associated exonuclease activity. Mirin inhibits MRN-dependent activation of ATM. |
- NAR Cancer, 2022, 4(2):zcac012
- Mol Cell, 2021, S1097-2765(21)00390-7
- Mol Cancer Ther, 2021, 20(9):1561-1571
|
|
S8375 |
AZD0156
|
AZD0156 is a potent and selective inhibitors of ATM kinase, with potential chemo-/radio-sensitizing and antineoplastic activities. AZD0156 prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells. |
- Sci Transl Med, 2022, 14(638):eabc7480
- Cell Rep, 2022, 38(2):110216
- Int J Mol Sci, 2022, 23(7)3834
|
|
S8556 |
AZ31
|
AZ31 is a selective and novel ATM inhibitor with an IC50 of <0.0012 μM. It shows excellent selectivity over closely related enzymes (>500 fold selective over DNA-PK and PI3Kα and >1000 fold selective over mTOR, PI3Kβ and PI3Kγ). |
- Proc Natl Acad Sci U S A, 2020, 117(50):31891-31901
|
|
S8666 |
Elimusertib (BAY-1895344) hydrochloride
|
Elimusertib (BAY-1895344) hydrochloride is a potent, highly selective and orally available ATR inhibitor with an IC50 of 7 nM. |
- Clin Cancer Res, 2021, clincanres.1010.2021
- Cancer Res, 2021, 81(18):4676-4684
- Cancer Discov, 2021, 11(2):362-383
|
|
S8680 |
AZD1390
|
AZD1390 is a first-in-class orally available and CNS penetrant ATM inhibitor with an IC50 of 0.78 nM in cells and >10,000-fold selectivity over closely related members of the PIKK family of enzymes and excellent selectivity across a broad panel of kinases. |
- Cancer Cell, 2022, S1535-6108(21)00662-0
- Sci Transl Med, 2022, 14(638):eabc7480
- Nucleic Acids Res, 2022, 50(5):2700-2718
|
|
S8729 |
AZ32
|
AZ32 is a specific inhibitor of the ATM kinase that possesses good BBB penetration in mouse with an IC50 value of <0.0062 μM for ATM enzyme. It shows adequate selectivity over ATR and also has high cell permeability. |
|
|
S9639 |
VX-803 (M4344)
|
VX-803 (M4344, ATR inhibitor 2) is an ATP-competitive, orally active, and selective inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase with Ki of < 150 pM. VX-803 (M4344) potently inhibits ATR-driven phosphorylated checkpoint kinase-1 (P-Chk1) phosphorylation with IC50 of 8 nM. VX-803 (M4344) exhibits potential antineoplastic activity. |
|
|
S9864 |
Elimusertib (BAY-1895344)
|
Elimusertib (BAY-1895344) is a very potent and highly selective ATR (ataxia telangiectasia and Rad3-related) inhibitor with IC50 of 7 nM. Elimusertib potently inhibits proliferation of a broad spectrum of human tumor cell lines with median IC50 of 78 nM. |
- J Med Chem, 2022, 65(5):4182-4200
- Sci Rep, 2022, 12(1):5827
- Nat Commun, 2021, 12(1):6813
|
|